TIE2-mediated tyrosine phosphorylation of H4 regulates DNA damage response by recruiting ABL1.

TitleTIE2-mediated tyrosine phosphorylation of H4 regulates DNA damage response by recruiting ABL1.
Publication TypeJournal Article
Year of Publication2016
AuthorsHossain MB, Shifat R, Johnson DG, Bedford MT, Gabrusiewicz KR, Cortes-Santiago N, Luo X, Lu Z, Ezhilarasan R, Sulman EP, Jiang H, Li SSC, Lang FF, Tyler J, Hung M-C, Fueyo J, Gomez-Manzano C
JournalSci Adv
Volume2
Issue4
Paginatione1501290
Date Published2016 04
ISSN2375-2548
KeywordsAngiotensin I, Cell Line, Tumor, DNA Damage, DNA End-Joining Repair, Histones, Humans, Protein Binding, Protein Transport, Proto-Oncogene Proteins c-abl, Radiation Tolerance, Radiation, Ionizing, Receptor, TIE-2, Tyrosine
Abstract

DNA repair pathways enable cancer cells to survive DNA damage induced after genotoxic therapies. Tyrosine kinase receptors (TKRs) have been reported as regulators of the DNA repair machinery. TIE2 is a TKR overexpressed in human gliomas at levels that correlate with the degree of increasing malignancy. Following ionizing radiation, TIE2 translocates to the nucleus, conferring cells with an enhanced nonhomologous end-joining mechanism of DNA repair that results in a radioresistant phenotype. Nuclear TIE2 binds to key components of DNA repair and phosphorylates H4 at tyrosine 51, which, in turn, is recognized by the proto-oncogene ABL1, indicating a role for nuclear TIE2 as a sensor for genotoxic stress by action as a histone modifier. H4Y51 constitutes the first tyrosine phosphorylation of core histones recognized by ABL1, defining this histone modification as a direct signal to couple genotoxic stress with the DNA repair machinery.

DOI10.1126/sciadv.1501290
Alternate JournalSci Adv
PubMed ID27757426
PubMed Central IDPMC5065225
Grant ListP30 CA016672 / CA / NCI NIH HHS / United States
R01 CA079648 / CA / NCI NIH HHS / United States
R01 CA095641 / CA / NCI NIH HHS / United States
R01 NS069964 / NS / NINDS NIH HHS / United States
P50 CA127001 / CA / NCI NIH HHS / United States
Related Faculty: 
Jessica K. Tyler, Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700